The objectives of this proposal are to better define the cellular events associated with impaired contraction and relaxation of myocardial tissue during hypoxia and to determine the relative importance of these events in influencing the degree of reversibility of an hypoxic insult. Two experimental models will be used in these studies: (1) monolayers of cultured chick embryo ventricle and (2) strips of intact chick embryo ventricle. In these preparations, alterations in contraction and relaxation may be correlated with changes in ion fluxes, intracellular ion activities, and high energy phosphate content during and after recovery from oxygen deprivation. The goals of these studies will be to: (1) determine if alterations in sodium-calcium exchange during hypoxia and recovery from hypoxia play a role in alteration of contraction and relaxation processes; (2) if enhanced Ca entrance into cells by Na-Ca exchange contributes to the irreversibility of hypoxic injury; (3) if irreversible damage to the Na ion-K ion-ATPase membrane pump is a necessary precursor to irreversible myocardial cell damage during hypoxia; and (4) the importance of limitation of oxygen diffusion in the interstitial space of intact ventricular tissue in altering apparent sensitivity of the myocardial cells to hypoxia. Further studies will be directed toward determining if improved diffusion of oxygen in the interstitial space is a mechanism of action of some agents which limit ischemic injury in intact tissue.